ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 19

The Lymphocyte Repertoire in Juvenile Dermatomyositis

Kacie Hoyt1, Edwin Anderson1,2, Megan L. Curran3, Robert Fuhlbrigge4, Luigi Notarangelo5, Lauren M. Pachman6, Susan Kim7 and Lauren Henderson8, 1Division of Immunology, Boston Children's Hospital, Boston, MA, 2Clinical Research Center/Rheumatology, Boston Children's Hospital, Medford, MA, 3Pediatric Rheumatology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, 4Children's Hospital Colorado, Aurora, CO, 5National Institute of Allergy and Infectious Diseases, Bethesda, MD, 6Cure JM Program of Excellence in Juvenile Myositis Research, Stanley Manne Children’s Research Institute, affiliated with Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, 7Pediatric Rheumatology, University of California, San francisco School of Medicine, San Francisco, CA, 8Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA

Meeting: 2017 Pediatric Rheumatology Symposium

Keywords: B cells, T cells and juvenile dermatomyositis

  • Tweet
  • Email
  • Print
Session Information

Date: Thursday, May 18, 2017

Session Title: Genetics and Pathogenesis Poster Breakout I

Session Type: Abstract Submissions

Session Time: 4:45PM-5:15PM

Background/Purpose: In adult dermatomyositis (DM), clonal populations of T and B cells with shared variable (V) gene usage have been identified in affected muscle, suggesting aberrant lymphocyte responses to a common antigen.  Using next generation sequencing (NGS), we aimed to determine if these previously identified repertoire abnormalities in the muscle of adult DM patients could be detected in the peripheral blood (PB) of children with juvenile DM (JDM). 

Methods: PB was obtained from JDM patients with skin and muscle disease (classic JDM) at diagnosis, during active disease, and at remission when patients were off medication.  Amyopathic patients and healthy controls were also studied.  CD8+ T and CD19+ B cells were isolated from PB mononuclear cells (PBMC) by magnetic beads.  The remaining lymphocyte populations were isolated by fluorescence activated cell sorting:  CD4/CD8 naïve (N) T cells (C3+CD4+/CD8+CD45RA+CCR7+), CD4/ CD8 memory (M) T cells (CD3+CD4+/CD8+CD45RA–), Treg cells (CD3+CD4+CD25+CD127lo), Teff cells (CD3+CD4+CD25–), Naïve B cells (CD19+IgD+CD27–), and CD21lo B cells (CD19+CD21loCD38lo).   The TCR β (TRB) and BCR heavy (IgH) chains were amplified by multiplex PCR with a standard quantity of genomic DNA serving as the template (ImmunoSEQTM).  Illumina HiSeq platform was used for sequencing.  Productive sequences were analyzed using the ImmunoSEQ set of online tools.  Mann Whitney and 1-way ANOVA tests were used to compare the clonality index, Shannon entropy, and clone sharing in study groups.  2-way ANOVA with Bonferroni correction was used to compare TCRVβ family usage.    

Results: Clinical characteristics of the patients are in Table 1.  CD21lo B cells, a population of B cells associated with autoimmunity, were more clonal in classic JDM patients with active disease compared to those in remission (p=0.03).  Similarly, the Treg repertoire was significantly more clonal in classic JDM patients with active disease than JDM patients in remission (p<0.0001) and amyopathic patients (p=0.002).   CD19, CD19N, CD8, CD4/8 N/M, and Teff cells were polyclonal and diverse in all JDM patient groups.  In Treg and Teff subsets, TCRVβ families 7, 10, and 28 were used more and Vβ families 3, 5, and 19 were used less in classic JDM patients with active disease compared to controls (p<0.0001for Treg and Teffs).  Inter-individual sharing of Teff clonotypes was observed in JDM patients with active disease compared to controls (p<0.001).   

Conclusion: Clonal expansions in CD21lo B and Treg cells noted in JDM patients with active disease resolved upon remission. Skewed TCRVβ family usage was observed in active JDM patients with increased usage of Vβ7, a Vβ family that has been linked with other autoimmune conditions.  Inter-individual sharing of Teff clonotypes was also observed.  Our pilot results suggest that lymphocyte repertoire abnormalities may contribute to disease pathogenesis in JDM and can be detected in PB by NGS. 

 


Disclosure: K. Hoyt, None; E. Anderson, None; M. L. Curran, None; R. Fuhlbrigge, None; L. Notarangelo, None; L. M. Pachman, None; S. Kim, None; L. Henderson, None.

To cite this abstract in AMA style:

Hoyt K, Anderson E, Curran ML, Fuhlbrigge R, Notarangelo L, Pachman LM, Kim S, Henderson L. The Lymphocyte Repertoire in Juvenile Dermatomyositis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 4). https://acrabstracts.org/abstract/the-lymphocyte-repertoire-in-juvenile-dermatomyositis-2/. Accessed May 19, 2022.
  • Tweet
  • Email
  • Print

« Back to 2017 Pediatric Rheumatology Symposium

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-lymphocyte-repertoire-in-juvenile-dermatomyositis-2/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2022 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.